rs17761734

Variant names:

• chr17-2205559-C-T
• rs17761734
• NM_017575.5:c.2870-17044G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017575.5(SMG6):​c.2870-17044G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,044 control chromosomes in the GnomAD database, including 1,302 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1302 hom., cov: 31)
• Consequence: SMG6 NM_017575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.382
• Publications: 8 publications found

Genes affected

SMG6 (HGNC:17809): (SMG6 nonsense mediated mRNA decay factor) This gene encodes a component of the telomerase ribonucleoprotein complex responsible for the replication and maintenance of chromosome ends. The encoded protein also plays a role in the nonsense-mediated mRNA decay (NMD) pathway, providing the endonuclease activity near the premature translation termination codon that is needed to initiate NMD. Alternatively spliced transcript variants encoding distinct protein isoforms have been described. [provided by RefSeq, Feb 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017575.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMG6	NM_017575.5	MANE Select	c.2870-17044G>A		intron	N/A	NP_060045.4
	SMG6	NM_001256827.2		c.146-17044G>A		intron	N/A	NP_001243756.1
	SMG6	NM_001256828.1		c.146-17044G>A		intron	N/A	NP_001243757.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMG6	ENST00000263073.11	TSL:1 MANE Select	c.2870-17044G>A		intron	N/A	ENSP00000263073.5
	SMG6	ENST00000354901.8	TSL:1	c.146-17044G>A		intron	N/A	ENSP00000346977.4
	SMG6	ENST00000536871.6	TSL:2	c.146-17044G>A		intron	N/A	ENSP00000440283.2

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16809 AN: 151926 Hom.: 1301 Cov.: 31

Gnomad AFR AF: 0.0284

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0455

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.141

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.111 AC: 16809 AN: 152044 Hom.: 1302 Cov.: 31 AF XY: 0.108 AC XY: 8009 AN XY: 74314

African (AFR) AF: 0.0284 AC: 1176 AN: 41480

American (AMR) AF: 0.121 AC: 1852 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 661 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5178

South Asian (SAS) AF: 0.0459 AC: 221 AN: 4812

European-Finnish (FIN) AF: 0.111 AC: 1175 AN: 10550

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11310 AN: 67976

Other (OTH) AF: 0.141 AC: 297 AN: 2110

Alfa AF: 0.123 Hom.: 1133

Bravo AF: 0.108

Asia WGS AF: 0.0210 AC: 74 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.40
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17761734; hg19: chr17-2108853;